Integrin expression and adhesivity to fibronectin in primary acute myeloid leukemia cells: Impact of NPM1 and FLT3 mutations

Objectives Interaction of leukemia cells with the bone marrow extracellular matrix promotes cell survival and resistance to chemotherapy. In this work, we analyzed integrin expression and adhesivity to fibronectin in primary cells from patients with acute myeloid leukemia. Methods Surface expression of integrins beta 1 and alpha V beta 3 on primary leukemia cells (N = 46) was correlated with the stem cell marker CD34, as well as with cell adhesivity to fibronectin. The results were analyzed with regard to the mutational status ofNPM1andFLT3genes. Results The integrin beta 1 was omnipresent, whereas alpha V beta 3 was often more expressed on CD34-positive cells. In particular, higher alpha V beta 3 expression on CD34+ cells was associated withNPM1mutation (P = .0018). Monocytic leukemias had significantly higher alpha V beta 3 expression compared to less maturated cases (P = .0008). Cells from patients with internal tandem duplications inFLT3(FLT3-ITD) had lower adhesivity to fibronectin compared to cells with wild-typeFLT3(P = .031), specifically in less differentiated myeloblasts. Inhibition of a putative FLT3-ITD target, EZH2, increased cell adhesivity in MV4-11 cell line (P = .024). Conclusions The integrin alpha V beta 3 is expressed in particular on CD34+ cells withNPM1mutation and might have a prognostic value in patients with mutatedNPM1. FLT3-ITD is associated with lower cell adhesivity, especially in patients with less differentiated leukemias.